Cytochromes P-450 and P-448 are the membrane bound terminal oxidases responsible for the metabolism of drugs and carcinogens in mammalian liver. These cytochromes are located within the membrane of the smooth endoplasmic reticulum in several molecular forms with different chemical, physical and biological properties. These include substrate specificity, ligand binding equilibria and kinetics, molecular weight, spectral, and immunologic properties. The goal of this research is to determine the mechanism of ligand binding to these various forms and to correlate changes in the kinetics and equilibrium constants measured with changes in the physical properties of the cytochromes induced by solubilization, purification, incorporation into detergent micelles and phospholipid vesicles, and by interaction with substrates and other proteins of the hydroxylating system.